Paramyxovirus vector

Abstract

An objective of the present invention is to provide an improved negative-strand RNA viral vector and a use thereof, the negative-strand RNA viral vector exhibiting transient high expression of genes loaded in the vector and enabling the rapid removal of the vector after said expression. It was discovered that by adding a micro-RNA target sequence to the NP, P, or L gene of a negative-strand RNA viral vector, it is possible to control the expression of the vector depending on the micro-RNA expressed by the introduction cell. In particular, when a micro-RNA target sequence was added to the NP or P gene, the expression of the vector decreased depending on the micro-RNA, and the removal of the vector was promoted, while the effect was reversed when a micro-RNA target sequence was added to the L gene. The vector can be applied in cell therapy and regenerative medicine and can be used as a therapeutic vector that targets cancer.

The invention claimed is: 
     
       1. A modified Sendai virus vector, which comprises two P genes, wherein
 a first P gene encodes a first P protein which comprises D433A, R434A, K437A, and L511F substitutions and is temperature sensitive, and further has a degron, and 
 a second P gene has a target sequence of a microRNA in its coding region or 5′- or 3′-noncoding region, and a P protein encoded by the second P gene does not contain a temperature sensitive mutation and is functionally expressed at 37° C. 
 
     
     
       2. The modified Sendai virus vector according to  claim 1 , wherein the microRNA is miR143 and the degron is a mODC PEST degron.